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生物活性タンパク質スイッチの新規設計
Robert A Langan1,2,3, Scott E Boyken1,2, Andrew H Ng4,5,6,7
1Department of Biochemistry, University of Washington, Seattle, WA, USA.
Nature
|July 26, 2019
PubMed で要約を見る
まとめ
科学者は競合する相互作用を制御することで 交換可能なタンパク質システムを設計しました これらの設計されたタンパク質のケージと鍵は タンパク質の機能に対する誘導制御を可能にし 合成生物学を前進させています
科学分野:
- タンパク質工学
- 合成生物学
- 生物化学
背景:
- アロステリック調節は生物学的に重要ですが,デノボのタンパク質設計で達成するのは困難です.
- 多重でエネルギー的に類似した状態を持つタンパク質を 設計することは大きな課題です
研究 の 目的:
- 交換可能なタンパク質システムのデザインを 探求する
- タンパク質の機能を 相互に競合する分子間相互作用で調節する
- ケージ・ラッチ・キーメカニズムを使って 誘導可能なタンパク質システムを作ります
主な方法:
- 静的な5ヘリクスのタンパク質ケージを設計し,単一のインタラクションインターフェースを使用しました.
- 分子内部で相互作用したり, 分子間の"キー"ペプチドによって 置き換えられるような"ラッチ"ヘリクスを設計した.
- 機能的なモチーフ (結合,分解,核輸出) がロックヘリックスに組み込まれています.
主要な成果:
- 交換可能なタンパク質の機能を証明する オートゴーナルケージキーシステムを開発した.
- 検証された機能性 in vitro,酵母,そして哺乳類の細胞.
- 錠前を鍵で動かすと タンパク質機能が40倍まで活性化します
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